The present invention relates to the software and systems for high throughput micro fluidic analysis. More specifically, the invention relates to computer implemented processes for data analysis as well as graphical user interface techniques for directing and analyzing data from high throughput microfluidic systems.
Considerable work is now underway to develop microfluidic systems, particularly for performing chemical, clinical and environment analysis of chemical and biological specimens. The term xe2x80x9cmicrofluidicxe2x80x9d refers to a system or device having one or a network of chambers and/or channels, which have micro scale dimensions, e.g., having at least one cross sectional dimension in the range from about 0.1 xcexcm to about 500 xcexcm. Microfluidic substrates are often fabricated using photolithography, wet chemical etching, injection molding, embossing, and other techniques similar to those employed in the semiconductor industry. The resulting devices can be used to perform a variety of sophisticated chemical and biological analytical techniques.
Micro fluidic analytical systems have a number of advantages over conventional chemical or physical laboratory techniques. For example, microfluidic systems are particularly well adapted for analyzing small sample sizes, typically making use of samples on the order of nanoliters and even picoliters. The channel defining substrates may be produced at relatively low cost, and the channels can be arranged to perform numerous analytical operations, including mixing, dispensing, valving, reactions, detections, electrophoresis, and the like. The analytical capabilities of microfluidic systems are generally enhanced by increasing the number and complexity of network channels, reaction chambers, and the like.
Substantial advances have recently been made in the general areas of flow control and physical interactions between the samples and the supporting analytical structures. Flow control management may make use of a variety of mechanisms, including the patterned application of voltage, current, or electrical power to the substrate (for example, to induce and/or control electrokinetic flow or electrophoretic separations). Alternatively, fluid flows may be induced mechanically through the application of differential pressure, acoustic energy, or the like. Selective heating, cooling, exposure to light or other radiation, or other inputs may be provided at selected locations distributed about the substrate to promote the desired chemical and/or biological interactions. Similarly, measurements of light or other emissions, electrical/electrochemical signals, and pH may be taken from the substrate to provide analytical results. As work has progressed in each of these areas, the channel size has gradually decreased while the channel network has increased in complexity, significantly enhancing the overall capabilities of microfluidic systems.
One particularly advantageous application for microfluidic techniques is to screen collections of large numbers of samples. There has long been a need to rapidly assay numerous compounds for their affects on various biological processes. For example, enzymologists have long sought improved substrates, inhibitors, and/or catalysts for enzymatic reactions. The pharmaceutical industry has focused on identifying compounds that may block, reduce, or enhance the interactions between biological molecules, such as the interaction between a receptor and its ligand. The ability to rapidly process numerous samples for detection of biological molecules relevant to diagnostic or forensic analysis could also have substantial benefits for diagnostic medicine, archaeology, anthropology, and modem criminal investigations. Modem drug discovery has long suffered under the limited throughput of known assay systems for screening collections of chemically synthesized molecules and/or natural products. Unfortunately, the dramatic increase in the number of test compounds provided by modem combinatorial chemistry and human genome research has overwhelmed the ability of existing techniques for assaying sample compounds.
High throughput screening assay systems and methods have been previously described in for example, published PCT Patent Application No. WO 98/00231, U.S. Pat. No. 5,779,868 and U.S. Pat. No. 5,942,443, which are all hereby incorporated by reference for all purposes. These patents and applications describe, among other things, a microlaboratory system that can sequentially introduce a large number of test compounds (typically contained in a multiwell plate) into a large number of assay chips or microfluidic devices. This advantageous system allows testing of a large number of sample compounds with a compact sample handling arrangement, while the manipulation of picoliter or nanoliter volumes of chemicals can both enhance the speed of each chemical analysis and minimize and sample and waste product volumes. Hence, such a microlaboratory system represents a significant advancement for handling and testing large numbers of chemical and biological compounds.
Nevertheless, it would be beneficial to have innovative techniques for identifying sample compounds that demonstrate an effect during assay processing and preferably, ways of verifying the accuracy of the measured effect and/or identified sample compound. Additionally, it would be beneficial to have innovative software and systems that would allow the researcher to more easily direct the operation of the high throughput microfluidic system and greater flexibility in analyzing the data acquired by the high throughput microfluidic system.
The present invention provides innovative software and systems for analyzing data from and directing the operation of high throughput microfluidic systems. In one aspect of data analysis, a signal is analyzed to identify sample compounds that demonstrate an observed effect on a reaction. The effect can also be verified by further analysis. In one aspect of system direction, users can configure the high throughput microfluidic systems by entering information utilizing a graphical user interface. For example, the user can specify the sample plate that is being utilized, set dwell times for sample compounds and buffer solutions, specify characteristics for dye fluids, specify characteristics for guard fluids, set sample dilution parameters, and the like. Additionally, the user can view a graph of measured signal strength as sample compounds flow past the detection point of a microfluidic device while viewing information relating to a script that directs the flow of the system and observing values for channels specified by the script. Some embodiments are described below.
In one embodiment, the invention provides a computer implemented method of analyzing an array of sample compounds utilizing a microfluidic device. A signal corresponding to sample compounds being driven through the microfluidic device are received. The signal is analyzed to detect a deviation. The sample compound that caused the deviation is then identified. The deviation can be the result of, for example, an inhibitor or an enhancer of an enzymatic reaction.
In another embodiment, the invention provides a computer implemented method of analyzing an array of sample compounds utilizing a microfluidic device. User input specifying a dwell time for the sample compounds is received. Also, user input specifying a dwell time for a buffer solution is received. The sample compounds and buffer solution are then alternatingly injected into the microfluidic device for the specified dwell times for the sample compounds and buffer solution. In preferred embodiments, the microfluidic device includes at least two intersecting channels with a cross sectional dimension in a range of about 0.1 xcexcm to about 500 xcexcm.
In another embodiment, the invention provides a computer implemented method of analyzing an array of sample compounds utilizing a microfluidic device. A graph of a measured signal strength as the sample compounds flow past a detection point of the microfluidic device is displayed. Information relating to a script that directs the flow of the sample compounds past the detection point is also displayed. A value for a channel specified by the script is displayed and in preferred embodiments, a user can enter a formula that will be calculated so that the result can be displayed.